There is increasing evidence supporting a possible role for C. pneumonia in the pathogenesis of coronary atherosclerosis and its complications. This evidence stems from the results of seroepidemiologic studies, indicating an association between C. pneumonia seropositivity and coronary heart disease (CHD) and from microbiologic studies, indicating that C. pneumonia may be detected in a large proportion of atherosclerotic plaque specimens. The preliminary results of two human treatment trials, which have been recently published, suggest that treatment with antibiotics activate against C. pneumonia may be effective in secondary prevention of cardiovascular events. The strength of the evidence currently available in support of a role for C. pneumonia in the pathogenesis of atherosclerosis, and the magnitude of the potential public health importance of this finding, support further research involving clinical treatment trials of patients with atherosclerotic cardiovascular disease. The proposed study is a randomized, double-blind trial of azithromycin vs. placebo among adults with documented prevalence coronary artery disease. Patients will be treated for one year and followed for a mean of 3.75 years (range 3.0 to 4.5 years) for the composite primary study outcome of CHD death, non- fatal myocardial infarction, hospitalization for unstable angina, and requirement for revascularization procedures. Completed follow-up of 3500 subjects will provide 95 percent power to detect a 25 percent decrease, and 80 percent power to detect a 20 percent decrease, in the rate of the primary outcome in the treatment group, assuming a 6.5 percent per year event rate in the placebo group. Serologic testing for C. pneumonia will be performed on all subjects at enrollment and at intervals during the follow-up period for a random 25 percent of subjects. The results of this study will provide important information on the potential role of antibiotic therapy for the secondary prevention of complication of coronary artery disease.